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Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
Chromatin remodeler Fun30 facilitates the relocation of persistent DNA double-strand breaks to the nuclear periphery
Mehwish Iqbal1,2, Jisha Chalissery1, Amira Bekdash1
1Department of Biochemistry and Molecular Biology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
Abstract:
DNA double-strand break (DSB) repair is critical for genome stability and requires chromatin remodeling for efficient processing. Fun30, an ATP-dependent chromatin remodeler, promotes long-range DNA end resection to generate 3' overhangs, a key step in homologous recombination. Persistent DSBs relocate to the nuclear periphery, particularly through interactions with the inner nuclear membrane protein Mps3 and the nuclear pore complex component Nup84. By tracking a single irreparable break, we show that Fun30 facilitates this relocation. In fun30Δ cells, Mps3 and Nup84 enrichment at DSBs was reduced, indicating impaired tethering. We further demonstrate that Fun30 promotes deposition of the histone variant H2A.Z at DSBs. Thus, Fun30 favors relocation of persistent DSBs to the nuclear periphery by supporting resection and H2A.Z incorporation.
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